Species-specific gamete recognition initiates fusion-driving trimer formation by conserved fusogen HAP2

Jun Zhang, Jennifer F. Pinello, Ignacio Fernández, Eduard Baquero, Juliette Fedry, Félix A. Rey and William J. Snell ()
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Jun Zhang: University of Maryland
Jennifer F. Pinello: University of Maryland
Ignacio Fernández: Unité de Virologie Structurale, Virology Department and CNRS UMR 3569, Institut Pasteur
Eduard Baquero: Unité de Virologie Structurale, Virology Department and CNRS UMR 3569, Institut Pasteur
Juliette Fedry: Unité de Virologie Structurale, Virology Department and CNRS UMR 3569, Institut Pasteur
Félix A. Rey: Unité de Virologie Structurale, Virology Department and CNRS UMR 3569, Institut Pasteur
William J. Snell: University of Maryland

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: Abstract Recognition and fusion between gametes during fertilization is an ancient process. Protein HAP2, recognized as the primordial eukaryotic gamete fusogen, is a structural homolog of viral class II fusion proteins. The mechanisms that regulate HAP2 function, and whether virus-fusion-like conformational changes are involved, however, have not been investigated. We report here that fusion between plus and minus gametes of the green alga Chlamydomonas indeed requires an obligate conformational rearrangement of HAP2 on minus gametes from a labile, prefusion form into the stable homotrimers observed in structural studies. Activation of HAP2 to undergo its fusogenic conformational change occurs only upon species-specific adhesion between the two gamete membranes. Following a molecular mechanism akin to fusion of enveloped viruses, the membrane insertion capacity of the fusion loop is required to couple formation of trimers to gamete fusion. Thus, species-specific membrane attachment is the gateway to fusion-driving HAP2 rearrangement into stable trimers.

Date: 2021
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DOI: 10.1038/s41467-021-24613-8

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